Tolerance to the luteinizing hormone and prolactin suppressive effects of delta-9-tetrahydrocannabinol develops during chronic prepubertal treatment of female rats.
Tolerance to the luteinizing hormone and prolactin suppressive effects of delta-9-tetrahydrocannabinol develops during chronic prepubertal treatment of female rats.
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发表时间：
1986-09
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通讯作者：
E. Field;L. Tyrey
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作者：
E. Field;L. Tyrey
为了确定青春期前的雌性大鼠是否对 δ-9-四氢大麻酚 (THC) 的激素抑制作用产生耐受性，我们测试了 THC (10 mg/kg 腹腔注射) 阻断青春期前重复使用 THC 的动物在第一次发情前期急剧激增的黄体生成素 (LH) 和催乳素 (PRL) 的能力。用 10 mg THC/kg b.wt 预处理大鼠。从 27 日龄开始每天两次，并将第一次发情前期 THC 治疗的阻断功效与之前未治疗或仅用药物载体预处理的动物进行比较。在30日龄时打开阴道，以便通过阴道涂片鉴定第一次发情前期，并在发情前期治疗之前和之后收集用于LH和PRL放射免疫测定的系列血样。在先前未经治疗或媒介物预处理的动物中，在第一次发情前期当天 1300 小时进行 THC 治疗抑制了下午 LH 和 PRL 的激增，而在发情前期 1300 小时仅注射媒介物的对照动物中发生了激素激增（P 小于 0.05）。相比之下，无论是在发情前期1300小时用THC还是媒介物治疗，用THC预处理的动物都表现出显着的LH和PRL激增。在发情前期仅接受媒介物的动物中，用THC预处理的组和用媒介物预处理的组之间的血清LH浓度或LH激增的时间没有差异。这些结果与长期接受 THC 治疗的青春期大鼠最终发生排卵的假设是一致的，因为对其促性腺激素抑制作用产生了耐受性。
To determine if prepubertal female rats develop tolerance to the hormone suppressive action of delta-9-tetrahydrocannabinol (THC), we tested the ability of THC (10 mg/kg i.p.) to block luteinizing hormone (LH) and prolactin (PRL) surges acutely at first proestrus in animals that were treated repetitively with THC before puberty. Rats were pretreated with 10 mg THC/kg b.wt. twice daily beginning at 27 days of age and the blocking efficacy of THC treatment at first proestrus was compared to that in animals that were previously untreated or were pretreated only with drug vehicle. Vaginae were opened at 30 days of age to permit identification of first proestrus by vaginal smears, and serial blood samples for LH and PRL radioimmunoassays were collected before and after treatment at proestrus. In previously untreated or vehicle-pretreated animals, THC treatment at 1300 hr on the day of first proestrus inhibited the afternoon surges of LH and PRL, whereas hormone surges occurred in control animals injected with only vehicle at 1300 hr proestrus (P less than .05). In contrast, animals pretreated with THC exhibited marked LH and PRL surges whether treated at 1300 hr proestrus with THC or vehicle. Among animals receiving only vehicle at proestrus, there was no difference in serum LH concentrations or in timing of the LH surge between the group pretreated with THC and the group pretreated with vehicle. These results are consistent with the hypothesis that ovulation eventually occurs in the pubertal rat treated chronically with THC because tolerance develops to its gonadotropin suppressive effects.